Fractional esterification rate of cholesterol in high density lipoprotein (HDL) can predict the particle size of low density lipoprotein and HDL in patients with coronary heart disease

Ohta, Takao; Saku, Keijiro; Takata, Kazuhide; Nagata, Noriyuki; Maung, Kyu Kyu; Matsuda, Ichiro

doi:10.1016/s0021-9150(97)00163-9

Cited by 30 publications

(20 citation statements)

References 37 publications

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“…These results are in agreement with previous reports of association of these "classic" markers with angiographically confirmed CAD (21 ). We have shown that FER HDL , an indirect measure of lipoprotein particle size (22)(23)(24), is a better predictor of positive angiographic findings than the classic markers. Recent reports confirmed that the smallest LDL (25 ) and small HDL (26 ) particles are most strongly related to coronary disease progression.…”

Section: Discussionsupporting

confidence: 93%

Fractional Esterification Rate of Cholesterol and Ratio of Triglycerides to HDL-Cholesterol Are Powerful Predictors of Positive Findings on Coronary Angiography

2003

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Background:We examined the predictive value of various clinical and biochemical markers for angiographically defined coronary artery disease (aCAD). Specifically, we assessed the value of the ratio of plasma triglyceride ( Results: Members of the aCAD(؉) group were older and had a higher incidence of smoking and diabetes than those in the aCAD(؊) group. The aCAD(؉) group also had higher TG, apoB, FER HDL , and log(TG/HDL-C) and lower HDL-C values. aCAD(؉) women had greater waist circumference and higher plasma TC and TC/ HDL-C. aCAD(؉) men, but not women, had higher plasma LDL-C. In the multivariate logistic model, the

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Section: Discussionsupporting

confidence: 93%

Fractional Esterification Rate of Cholesterol and Ratio of Triglycerides to HDL-Cholesterol Are Powerful Predictors of Positive Findings on Coronary Angiography

2003

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“…Earlier investigations have noted that LDL and HDL sizes are significantly correlated, [11][12][13][14] and the present study of Ͼ1100 subjects confirms that very strong correlation, accounting for Ϸ25% of the variance. These findings suggest a common pathway(s) that influences relative particle size distribution within the spectrum of possible sizes for LDLs and HDLs and for Lp(a) as well.…”

Section: Discussionsupporting

confidence: 88%

“…[11][12][13][14] Although triglyceride (TG) concentrations are associated with LDL and HDL size variation, recent results suggest that at least a portion of the correlation between LDL and HDL sizes is independent of TG levels. 15 These observations suggest the existence of a metabolic mechanism(s) that governs the coordinated covariation in the relative sizes of several classes of lipoproteins.…”

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confidence: 99%

Genetic Control of Coordinated Changes in HDL and LDL Size Phenotypes

Rainwater

Martin

Comuzzie

2001

ATVB

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Abstract-We investigated the correlation of high density lipoprotein (HDL) and low density lipoprotein (LDL) particle size distributions in samples from Ͼ1100 participants in the San Antonio Family Heart Study. By use of analyses of individual correlations of each HDL fraction with each LDL fraction, we devised new metrics for particle size phenotype, termed ⌬HDL and ⌬LDL, to optimally reflect the size correlations. Confirming previous studies, we found that the 2 size phenotype variables were positively correlated (rϭ0.51). Quantitative genetic analysis indicated that nearly half (44%) of the variance in ⌬HDL and in ⌬LDL was explained by the additive effects of genes. Bivariate genetic analyses indicated that a positive genetic correlation ( G ϭ0.56) exists between them and suggested that the pleiotropic effects of a gene or group of genes account for Ϸ31% [ie, G 2 ϭ(0.56) 2 ϭ0.31] of the genetic variance in the 2 traits. Triglyceride (TG) levels were negatively related to ⌬HDL and ⌬LDL, with phenotypic correlations of Ϫ0.48 and Ϫ0.58, respectively, and genetic correlations of Ϫ0.45 and Ϫ0.76, respectively, suggesting that genes exert significant pleiotropic effects on the covariation of TGs with each of the size variables. Finally, we evaluated a bivariate model for ⌬HDL and ⌬LDL in which TG level was included as a covariate. This analysis indicated that a small but significant genetic correlation remains for ⌬HDL and ⌬LDL, even after accounting for the effects of TGs. Thus, our study demonstrates that the phenotypic correlation of HDL and LDL sizes results in part from the pleiotropic actions of a set of genes, some of which also influence TG levels and some of which do not. Key Words: LDL size distributions Ⅲ HDL size distributions Ⅲ genetics Ⅲ triglycerides Ⅲ Mexican Americans L ipoprotein particles of differing sizes play distinct roles in lipoprotein metabolism and the process of atherosclerosis. The predominance of small dense LDLs was identified as a risk factor for cardiovascular disease (CVD), 1 and prospective studies now have confirmed this initial observation. 2-4 Several mechanisms have been proposed to explain this association 5 : (1) small dense LDLs are more readily converted to highly atherogenic oxidized LDLs; (2) they more readily bind to surface components in the vessel wall; and (3) their size permits a more efficient infiltration into the vessel wall.There is growing evidence that HDL subpopulations differ in their abilities to protect against CVD. 6,7 However, whether current methods of measuring HDL subpopulations provide a substantial increment in CVD-predictive power is more controversial. For example, 2 studies reported significant associations of small dense HDLs (ie, HDL 3 , separated by electrophoresis and density fractionation) and CVD, but they differed as to whether HDL 3 improved the prediction. 8,9 Using nuclear magnetic resonance methodology, Freedman et al 10 found that lipoprotein subpopulation measures, for HDL and LDL, significantly increased the proportion of variation ...

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“…However, as in adults, children with pattern B had more risk factors (atherogenic lipoprotein profile, adiposity, and insulin resistance) for CHD than children with pattern A. With respect to the correlates of LDL size in children, we previously reported positive associations with HDL-C, apoA-I, and fractional esterification rate in HDL, and a negative association with TG, although the number of subjects studied was small (18). In the present study, we confirmed the previous data and found that BMI, insulin resistance, and plasma concentrations of apoB, glucose, and insulin are also linked to LDL size in children.…”

Section: Discussionmentioning

confidence: 86%

“…Subjects with small, dense LDL have a 3-fold greater CHD risk (16). LDL particle size is associated with plasma triglyceride (TG), high-density lipoprotein (HDL) cholesterol (HDL-C), and fractional esterification rate in HDL (17,18). In addition, age, sex, body fat, insulin resistance, and environmental (diet etc.)…”

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confidence: 99%

Low-Density Lipoprotein Particle Size and Its Regulatory Factors in School Children

Shimabukuro

Sunagawa

Ohta

2004

The Journal of Clinical Endocrinology & Metabolism

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Small low-density lipoprotein (LDL) particles are more atherogenic than larger LDL particles. To help prevent atherosclerotic coronary heart diseases, it may be useful to understand risk factors during childhood. In the present study, we evaluated LDL size and its relationship to other risk factors for atherosclerotic coronary heart disease. LDL size was measured by 2-15% gradient gel electrophoresis in 586 Japanese children (316 boys and 270 girls). Plasma lipids, apolipoproteins (apo), glucose, and insulin were also determined by conventional methods.Pattern B (LDL size < 25.5 nm) was found in 10.8% of boys and 4.4% of girls. Children with pattern B had a higher body mass index (BMI) and insulin resistance and a more atherogenic lipoprotein profile [higher triglycerides, higher apoB, and lower high-density lipoprotein cholesterol (HDL-C)] than children with pattern A (LDL size > 25.5 nm). BMI, insulin resistance, and plasma concentrations of triglycerides, glucose, and insulin decreased and plasma concentrations of HDL-C and apoA-I increased as LDL size increased. HDL-C and insulin in boys, and BMI, HDL-C, and apoA-I in girls predicted 22.9 and 28.1% of the variability of LDL size, respectively.LDL size was correlated with BMI and plasma concentrations of HDL-C, apoA-I, and insulin. Although the contribution of these parameters to LDL size in children was less than that in adults, improvement of these parameters by changes in lifestyle might be important for preventing the development of atherosclerosis even in children. (J Clin Endocrinol Metab 89: 2923-2927, 2004) P LASMA LEVELS OF low-density lipoprotein (LDL) cholesterol (LDL-C) are positively associated with the risk for coronary heart disease (CHD) (1, 2). However, several studies have shown that 30 -40% of CHD patients have normal LDL-C levels (Ͻ 130 mg/dl) (3-5). LDL particles vary in size and hydration density (6, 7). Several LDL subfractions can be identified on gradient gel electrophoresis. Among these LDL subfractions, small LDL particles possess a lower binding affinity for cellular LDL receptor and are more easily oxidized in vitro (8 -11). These data suggest that small LDL particles are atherogenic because their lower binding affinity for LDL receptor reflects a longer plasma residence time for them to be oxidized and taken up by macrophages in extravascular spaces. In accordance with these in vitro data, several case-control studies have indicated that smaller LDL particles are predominant in a high proportion of CHD patients, even those with normal LDL-C levels (12-15). Subjects with small, dense LDL have a 3-fold greater CHD risk (16). LDL particle size is associated with plasma triglyceride (TG), high-density lipoprotein (HDL) cholesterol (HDL-C), and fractional esterification rate in HDL (17, 18). In addition, age, sex, body fat, insulin resistance, and environmental (diet etc.) and genetic factors have been reported to affect LDL particle size (14, 19 -21).As previously mentioned, the relationships between LDL size and other risk factors f...

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Fractional esterification rate of cholesterol in high density lipoprotein (HDL) can predict the particle size of low density lipoprotein and HDL in patients with coronary heart disease

Cited by 30 publications

References 37 publications

Fractional Esterification Rate of Cholesterol and Ratio of Triglycerides to HDL-Cholesterol Are Powerful Predictors of Positive Findings on Coronary Angiography

Fractional Esterification Rate of Cholesterol and Ratio of Triglycerides to HDL-Cholesterol Are Powerful Predictors of Positive Findings on Coronary Angiography

Genetic Control of Coordinated Changes in HDL and LDL Size Phenotypes

Low-Density Lipoprotein Particle Size and Its Regulatory Factors in School Children

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